Four different types of growth regulation of normal and neoplastic T cells have been recognized by us and others: 1) TCGF dependent normal and neoplastic T cells; 2) TCGF independent normal and neoplastic T cells; 3) normal and neoplastic T cells which initially require the factor, but on repeated incubation become factor independent; and 4) neoplastic T cells which appear to be dependent on biochemically distinct variants of TCGF. Clones of neoplastic TCGF dependent T cells have been developed that turn off TCGF production in response to glucocortical steroids. As a result, their proliferation is also drastically reduced. The addition of homogeneously purified TCGF prepared from the cell line in question overcomes the block in proliferation caused by the glucocorticoids. Thus, TCGF has autocrine activity and can promote growth of neoplastic cells. Considerable progress has also been made in characterizing the biochemically distinct variants of TCGF produced by several malignant T cell lines. The variants have a much more acidic pI and higher molecular weights than normal TCGF. The data suggest that these differences are neither post-translational modifications nor do they result from improper precursor processing, but differ in primary structure. The biological significance of these variants is being studied.